When sonic hedgehog goes dyskinetic

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Dyskinesias are involuntary muscle movements associated with long-term use of levodopa therapy (use of levodopa is not a certainty for developing dyskinesias, but there is an association). A better understanding of the underlying biology of dyskinesias is required in order to alleviate this condition for those affected by it.

Recently researchers have reported that an imbalance between dopamine levels (associated with levodopa treatment) and a protein called sonic hedgehog could be partly underlying the development of dyskinesias.

In today’s post, we will explore what sonic hedgehog does in the body, provide an overview of dyskinesias, review the new research, and discuss the implications of the research.

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The humble fly (Drosophila). Source: Ecolab

No one should ever be allowed to say that fly geneticists don’t have a sense of humour.

When it comes to the naming of genes, these guys are the best!

A gene is a section of DNA that provides the instructions for making a particular protein, and each gene has been given a name. Some names are just boring – such as leucine-rich repeat kinase 2 (or LRRK2) – while other names are rather amusing. Especially the fly genes.

For example, there is one fly gene called “indy”, which stands for I‘m Not Dead Yet. Flies with genetic variation in this gene have longer than average lifespans (Click here to read more about this):

Source: Sciencemag

Another amusingly named gene is “Cheap Date”. Flies with a genetic mutation in this gene are very susceptible to alcohol (Click here to read more about this):

Source: Lordsofthedrinks

There is also “Ken and Barbie” – genetic variations in this gene result in a lack of external genitalia (Click here to read more about this).

The fly research community have a lot of really great names for genes: lunatic fringe”, “headcase” and “mothers against decapentaplegia (MAD)”

But one of the most popular gene names in all of biology is a gene called “Sonic Hedgehog”

What is Sonic Hedghog?

Continue reading “When sonic hedgehog goes dyskinetic”

Because I’m all about that base

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You may not realise it, but the DNA in your cells is under constant attack.

All kinds of stressors (like the damaging effects of oxidative stress resulting from cellular processes) are constantly bombarding this precision molecule that contains the genetic blueprint for making and maintaining you.

Luckily, millions of years of evolution has led to a complex and comprehensive DNA repair system that never takes holidays…. but might become a little slower as we age.

Recently researchers have reported that certain aspects of this DNA repair system could be playing a role in Parkinson’s. In today’s post, we will review some new research in this area and consider the implications of the findings. 

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My daughter is entering the pre-teen years, and I am struggling with all the horrors that that age brings.

Having survived the ‘Terrible Twos’ and the ‘Three-nager’ phase, I have absolutely adored innocence and magic of years 4 to 8. They were delightful. The ninth year, however, has brought with it the ominous arrival of (for lack of a better word) sass.

It has also involved a departure from the childhood songs (think Disney’s Lion King, Frozen, or Moana hits), and the introduction of more modern music, like her current favourite Meghan Trainor’s All about that Bass (see video above).

The next decade $£%#!& terrifies me.

But Meghan’s song provides an appropriate background for the subject matter of today’s post: Base excision repair

(Yeah, I know that’s a strange segway, but I’m tired and lacking imagination tonight)

What is Base excision repair?

Continue reading “Because I’m all about that base”

Monthly Research Review – August 2021

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At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during August 2021.

The post is divided into 10 parts based on the type of research:

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So, what happened during August 2021?

In world news:

August 6th – SpaceX stacked the Super Heavy Booster 4 and Star Ship 20 (Click here to read more about this)

 

August 9th – The Intergovernmental Panel on Climate Change releases the first part of its Sixth Assessment Report, which concludes that the effects of human-caused climate change are now “widespread, rapid, and intensifying“.

 

August 13th – Gino Strada passed away – and shame on you if you don’t know who he is

 

August 15th – The 50th anniversary of Nixon closing the “gold window” to foreign countries and ‘temporarily‘ abandoning the Bretton Woods Agreement, removing the gold standard and starting a new age of fiat currencies.

 

August 28th – The world’s northernmost island – a small patch of land measuring 60 x 30 metres – was announced by scientists off the coast of Greenland. The name Qeqertaq Avannarleq is proposed, which means “the northernmost island” (original!).

In the world of Parkinson’s research, a great deal of new research and news was reported:

In August 2021, there were 765 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (8,101 for all of 2021 so far). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 4 pieces of Parkinson’s news

Continue reading “Monthly Research Review – August 2021”

When we talk about “disease modification”

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There is a lot of effort focused on developing therapies that are capable of “disease modification” in Parkinson’s…

…but what do we actually mean by this label?

In today’s post, we will explore the idea in more depth.

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Source: Martech

It is inconceivable, but we live in a world full of words that we don’t really know the meaning of.

For example: Travesty

For the longest time, I thought this word meant a tragedy or something very unfortunate. And I would use it in a sentence like “His death was such a travesty“. But it doesn’t mean tragic at all. Or even unfortunate. Rather, it refers to a mockery or parody; a distorted representation of something.

Another example is the word Peruse

I would use “peruse” in a sentence like “I am going into that bookshop to peruse the shelves“, because I thought that the word meant to skim or browse and that using it might make me sound erudite and sophisticated.

Source: BBC

But it doesn’t mean to skim or browse.

Peruse means to ‘examine or observe in depth“.

Similarly: Nauseous

I have often said “I feel nauseous“, but nauseous describes something that causes a feeling of nausea. It doesn’t refer to the feeling itself (The word nauseated means to be affected with nausea).

And at a recent session of bedtime story reading with my daughter, I noted on p.582 (first page of chapter 36) of the Harry Potter and the Goblet of fire, that Prof McGonagall ‘looked slightly nauseous‘. So I am not alone in making this mistake.

All of this leads me to the topic for today’s discussion: What do we actually mean by the words ‘disease modification’?

It is a label I use almost everyday with my job at Cure Parkinson’s, but it strikes me as one that we (everyone) don’t really fully grasp.

Ok, so what does disease modification mean to you?

Continue reading “When we talk about “disease modification””

RePOOPulating the gut

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The gastrointestinal system is teeming with life – billions and billions of microorganisms that play a critical role in not only your physiological wellbeing, but also your survival.

A lot of research has been conducted on how this biosphere changes as we age.

Recently researchers published a study indicating that transplantation of the gut bacteria from young mice can improve the brain and immune systems of aged mice.

In today’s post, we will explore how the bacteria in our guts affects us, review the new research, and consider the implication for Parkinson’s.

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Source: Youtube

Today’s post starts with goats.

In the late 1950s, the Australian Division of Tropical Pastures began introducing and evaluating tropical plants for use in the beef industry of Northern Australia. Among the most promising was a shrub from central and South America called Leucaena leucocephala (Leucaena).

Leucaena leucocephala. Source: Wikipedia

It looked like a winner – it grew like a weed and the cattle loved it – but there was just one small problem: Leucaena contains a toxic amino acid called “mimosine” which made the animals very sick.

I can imagine that the scientists involved with the introduction of Leucaena must have been thinking “Struth mate, I’m feeling like a fair dinkum, true blue drongo. What have we done?”

But one researcher – named Dr Raymond Jones – made an interesting observation while at a research meeting in Hawaii – goats on the island were eating Leucaena…. without getting sick.

Dr Raymond Jones. Source: Creation

Long story short, Dr Jones & colleagues worked out that a bacteria in the rumen (a special ‘stomach’ where the food is pre-digested by microbes in cattle, sheep and goats) of the animals in Hawaii was able to breakdown mimosine.

Subsequent transplantation of the bacteria (which was named Synergistes jonesii after Dr Jones) allowed goats and cattle in Australia to eat Leucaena, and they all lived happily ever after:

Title: Successful transfer of DHP-degrading bacteria from Hawaiian goats to Australian ruminants to overcome the toxicity of Leucaena.
Authors: Jones RJ, Megarrity RG.
Journal: Aust Vet J. 1986 Aug;63(8):259-62.
PMID: 3790013

This case represents a powerful example of how transplanting gut bacteria can result in positive outcomes.

Interesting, but what does this have to do with Parkinson’s?

Continue reading “RePOOPulating the gut”

Getting expansive about treg cells

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In cancer research, scientists have devised methods of extracting samples of blood from patients and then growing certain populations of cells in those samples. The isolated subpopulations  of cells can then be manipulated in cell culture, before they are then injected back into the patient.

This is a form of immunotherapy – artificially boosting the immune system to target specific disease-related pathology in the body.

Recently, researchers have been exploring this alternative form of immunotherapy in the context of Parkinson’s… with some interesting results.

In today’s post, we will look at review this new research and consider the implications in terms of future therapies for Parkinson’s.

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Source: lls

Some time back, a friend in oncology (cancer) research said to me that “we are about to cure all blood cancers“. It should be noted that this optimistic friend is a “glass is completely full” type.

How so?” I asked.

CAR T-cell technology is amazing. Really coming into bloom” they responded.

What is CAR T-cell technology?” I asked.

They explained that it is a kind of immunotherapy – a method of boosting the immune system to help us fight disease.

CAR T-cell approaches basically involve removing a sample of blood from a person with cancer, expanding specific populations of those cells in cell culture, genetically manipulating those cells, and then re-introducing them into the body. They also explained that there were lots of different versions of CAR T-cells, with all kinds of potential applications.

Cool” I said, sounding enthusiastic, but only half understanding what they were saying. My friend is an immunologist, and my summary here is a one sentence version of a 30 minute sermon.

But they are correct.

CAR T-cell technology is achieving really impressive results in cancer (Click here and here to read more about this topic).

Interesting. What does this have to do with Parkinson’s?

Continue reading “Getting expansive about treg cells”

Monthly Research Review – July 2021

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At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during July 2021.

The post is divided into 10 parts based on the type of research:

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So, what happened during July 2021?

In world news:

July 8th – The global death toll from COVID-19 surpassed 4 million lives (Click here to read more about this).

July 11th — Billionaire Sir Richard Branson flew really high. A new age of “space” tourism… blah, blah, blah.

July 20th Billionaire Jeff Bezos flew really high (yawn)… Seriously, these folks have accumulated vast fortunes and this is how they chose to spend their money?!?!?

July 22nd – Dawn Butler was forced to leave the UK House of Commons by order of the acting Deputy Speaker, after she made comments referring to the Prime Minister Boris Johnson as a liar. Two questions: 1.) Why did her peers not walk out in solidarity with her?  2.) Why did the deputy speaker not point out the obvious (“All politicians are by nature“). Yes, I am a cynic.

July 23rd  – the Tokyo Olympic games began.

July 29th – New Zealand-based Rocket Lab successfully reached orbit (actual space) – the 18th electron rocket to do so.

In the world of Parkinson’s research, a great deal of new research and news was reported:

In July 2021, there were 819 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (7,336 for all of 2021 so far). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 5 pieces of Parkinson’s news

Continue reading “Monthly Research Review – July 2021”

AC Immune acquires assets of AFFiRiS

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Alpha synuclein is considered to be an influential factor in Parkinson’s. It is a protein that accumulates and clumps together inside certain nerve cells in many cases of Parkinson’s.

Recently, clinical trials have attempted to target alpha synuclein that is floating around outside of cells. Some of the strategies focus on an approach called ‘immunotherapy’, which involves boosting the immune system to help remove the toxic form of this protein from the body.

This week, one biotech company – AC Immune – bought the Parkinson’s-associated immunotherapy assets off another biotech company – AFFiRiS – which has been developing a potential vaccine for Parkinson’s.

In today’s post, we will discuss what immunotherapy is, look at how AFFiRiS has been trying to apply it to Parkinson’s, and review what AC-Immune plans to do next.

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AC Immune is a a Switzerland-based biotech company that was foundered in 2003.

They are focused on “improving the lives of patients suffering from Alzheimer’s and other neurodegenerative diseases” (Source).

Their approach has primarily centered around the development of immunotherapy approaches. And this week they made a very interesting announcement.

What is immunotherapy?

Continue reading “AC Immune acquires assets of AFFiRiS”

Farnesol: The farnesylator of PARIS

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A build up of “PARkin Interacting Substrate” (or PARIS) protein has been proposed as one potential mediator of the pathology observed in some cases of Parkinson’s. The accumulation of this protein leads to the inhibition of a key protein called PGC-1α, which is a neuroprotective protein that helps to keep cells alive.

For sometime, researchers have been searching for molecules that can act as inhibitors of PARIS, in the hope that blocking PARIS would allow PGC-1α to act freely. Such an agent could have potential as novel treatment for Parkinson’s.

This week a research report was published that describes one possible PARIS inhibitor. It is called farnesol.

In today’s post, we will look at the biology behind PARIS, review the new report, and discuss what exactly is known about farnesol.

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Pont Royal et Musée d’Orsay. Source: Wikipedia

Paris has a special place in my heart for several reasons.

The main one: I proposed to my wife there on the Pont Royal.

We had planned a day out in London, but once we got down to Waterloo “for lunch at a special restaurant“, I surprised her with two Euro Star tickets and we were off on the train for Paris – just like that (I might look the hardened tough guy on the outside, but deep down I am really just a tragic romantic).

And that night, after “dinner at a special restaurant” shortly before 10pm as we were crossing the middle of the Pont Royal, and a small miracle occurred: the traffic lights stopped traffic in both directions.

Source: Pixels

Seizing our chance moment alone, I dropped to one knee and asked (read: begged).

Now, if she had said ‘no thanks‘, I had a back up plan: Jump over the side of the bridge, float down the Seine some ways, climb out and then join the Foreign Legions the next day as a mute (je suis muet”).

But she didn’t say no (let’s call that the second small miracle) and thankfully for my fragile ego’s sake there wasn’t a lengthy deliberation.

When the traffic lights changed and traffic started to flow again, we received some enthusiastic honks of the klaxons (horns) as I got up and we headed off to alert our parents. It was a really nice moment.

I was recalling this moment, this week when a different type of Paris was being discussed in the news.

What do you mean “a different type of Paris”?

Continue reading “Farnesol: The farnesylator of PARIS”

The Bluerockers have started

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On the 8th June, BlueRock Therapeutics put out a press release announcing that the first participant in their Phase I clinical trial of cell transplantation for Parkinson’s had been dosed (Click here to read the press release).

The initiation of this clinical trial by the company is a major step forward for them and for the wider field of regenerative therapies.

In today’s post, we will look at what cell transplantation is, recent developments in clinical trials, and what the immediate future holds. 

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Source: The Scientist

Here on the SoPD, we work around the idea that any “curative therapy” for Parkinson’s is going to require three core components:

  1. A disease halting mechanism
  2. A neuroprotective agent
  3. Some form of restorative therapy

Parkinson’s is a progressive neurodegenerative condition, meaning that symptoms are gradually going to get worse over time. Thus, the first and most critical component of any ‘cure’ for Parkinson’s involves a treatment that will slow down or halt the progression of the condition.

Once such a therapy has been identified, it will be necessary to rejuvenate and protect the remaining cells. So, some form of neuroprotective therapy that can help bring sick or dying cells back to life will be required.

Such a treatment will also provide a nurturing environment for the third part of the ‘cure’: A restorative treatment. New cells will be required to replace the lost function.

Now, the bad news is (as far as I am aware) there is no single treatment currently available (or being tested) that can do all three of these things. By this I mean that there is no “disease halting mechanism” therapy that can also replace lost brain cells. Nor is there a restorative therapy that stop the progression of the condition.

That statement can obviously be read as terrible news, but it shouldn’t.

Let me explain:

Continue reading “The Bluerockers have started”